From:
`To:
`Subject:
`Date:
`Attachments:
`
`Richard Chen
`John West; Christian Haudenschild; Carol Tillis
`final board slides, ready for print
`Wednesday, October 31, 2012 1:40:06 PM
`board.11.01.12.v6.roc.ppt
`
`Hi Carol,
`
`These are ready for print. I didn't use the personalis template, do
`you want me to?
`
`Personalis EX2100
`
`
`To:
`Subject:
`Date:
`Attachments:
`
`Richard Chen
`John West; Christian Haudenschild; Carol Tillis
`final board slides, ready for print
`Wednesday, October 31, 2012 1:40:06 PM
`board.11.01.12.v6.roc.ppt
`
`Hi Carol,
`
`These are ready for print. I didn't use the personalis template, do
`you want me to?
`
`Personalis EX2100
`
`
`
`R&D Update
`
`Personalis, Inc.
`11.01.2012
`
`Richard Chen, CSO
`
`Personalis EX2100
`
`
`
`R&D Overview
`
`• Product Development
`• Content Development
`• Computing Infrastructure
`• Hiring
`
`Personalis EX2100
`
`
`
`Product Roadmap
`
`Clinical Dx Services & Genome
`Interpretation Services
`
`What are the disease risks?
`Which drugs should be avoided
`or dosed differently?
`
`Disease Variant Discovery Services (DVDS)
`
`What is the causative
`Genetic Variant?
`
`Personalis Genome Services (PGS)
`
`Current focus of
`development
`
`Sample Collection &
`DNA Extraction
`
`TTAGC…
`Whole
`Genome/Exome
`Sequence
`
`Alignment and
`Variant Calling
`
`Genes
`
`Pathways &
`Networks
`
`Diseases
`
`Drugs
`
`Clinical Dx
`
`Clinical
`Research
`(IRB)
`
`Discovery
`Research
`
`Personalis EX2100
`
`
`
`Personalis Genome Services for Research
`
`• Currently focused on PGS v1 development
`– In total ~80 features/enhancements, ~370 tasks
`– PRD updated, Continuing Agile development process
`– Winning the VA project has required reprioritizing and resourcing expanded set
`of features for v1
`– Key differentiating features include: Exome+, accuracy, SV detection, analytics
`leveraging proprietary content, unique visualization and enhanced reporting
`– Improving overall system performance optimization to better achieve
`throughput requirements of VA project and other large projects
`– 4 new hires have allowed us to catch up to our staffing requirements
`• Engaging early customers/collaborators including Moyamoya for early
`revenue, feedback and testing of our prototype service
`• PGS v1 service on track to launch at AGBT conference Feb 2012, First
`VA genomes will be processed around the same time
`• Submitted 6 talks to AGBT to support the PGS launch
`– Topics focus on key differentiators including accuracy, SV detection, proprietary
`content, and “success stories” applying our technology
`
`Personalis EX2100
`
`
`
`Exome Plus
`Review of Key Goals & Milestones
`
`• Problems with standard exome sequencing
`– Typical exome sequencing misses a lot of exome (not fully targeted, low coverage
`on high GC regions, other problematic regions)
`– Lots of biomedically interpretable content missed on standard exomes (regulatory
`regions, disease relevant variants in intergenic regions, intronic var)
`• The Personalis Exome Plus aims to solve these issues by augmenting
`standard exomes with custom pullout data
`• Milestones
`– Defined and prioritized High-value (Interpretable) Content
`– Defined and prioritized Top Exome Problematic regions
`– Designed and Received Enrichment Probes/Kits from Agilent
`– Next Steps
`– Evaluate first kits, refine spec and reorder
`– Refine cost model
`• Anticipate that this will be launched in 2 phases:
`– Targeting the first release as part of the PGS v1 launch in Feb 2013.
`– More research intensive parts of Exome Plus will be part of a 2nd release in 2013.
`
`Personalis EX2100
`
`
`
`Personalis Genome Services for Research
`Key Differentiated features in v1
`
`Sequencing
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`•
`
`•
`
`•
`
`•
`
`Exome and WGS with
`optimized sample prep
`
`Exome Plus capability
`extending standard
`exome coverage to
`biomedically important
`non-coding regions
`
`Exome Plus capability
`improves accuracy of
`standard exomes
`
`CLIA sequencing
`capability
`
`• State of the art pipeline
`resulting in better
`alignments, tested and
`optimized for accuracy
`and performance
`
`• Personalis enhanced
`reference genome for
`improved alignment and
`accuracy
`
`•
`
`Improved variant
`(SNP/Indel/SV) calling
`through integration of
`orthogonal methods to
`improve accuracy
`
`• Three high-quality,
`detailed, manually
`curated proprietary
`databases that enable
`genome annotation and
`analysis of complex
`disease, Mendelian
`disease,
`pharmacogenomics, and
`regulatory regions
`
`• Comprehensive genome
`annotation integrating and
`managing data from over
`30 public databases
`
`• Cutting edge analytics
`engine for case control
`analysis reveals
`statistically significant
`enrichment of genes,
`pathways, and diseases
`
`• Analytics powered by
`proprietary databases
`
`• Proprietary
`family/pedigree analysis
`and filtering methods
`
`• Comprehensive QC
`reporting for better
`accuracy assessment
`
`Personalis EX2100
`
`
`
`Personalis Genome Services for Research
`Key customer use cases addressed in PGS v1 Release
`
`Standard Seq & Pipeline
`
`Seq
`
`Lab
`
`Align
`
`Var
`Call
`
`DB
`Anno
`
`CLIA Seq and Pipeline
`
`Seq
`
`Lab
`
`Align
`
`Var
`Call
`
`DB
`Anno
`
`Population Case/Ctrl Studies
`
`Disease Cohort Study
`
`Complex Dz Case/Ctrl Study
`
`Pharma Case/Ctrl Study
`
`Tumor vs Normal Paired Case/Ctrl Studies
`
`Mendelian Dz Case/Ctrl Study
`
`Mendelian Multiple Trios Study
`
`Mendelian Large Pedigree
`
`Rare Pediatric Syndromes Dx
`(Trio etc)
`
`Diagnostic Panels
`
`PGS v1 Release
`
`Prototype Features at v1
`
`Genome Screening & Interpretation Service
`
`Discovery
`Research
`
`Clinical
`Research
`
`Clinical
`Diagnostics
`
`Personalis EX2100
`
`
`
`Summary of High-Level Timelines
`
`PGS Prototype ready
`
`PGS v1 Launch
`
`2012
`Apr
`
`May
`
`Jun
`
`Jul
`
`Aug
`
`Sept
`
`Oct
`
`Nov
`
`Dec
`
`2013
`Jan
`
`Feb
`
`Mar
`
`Spec
`
`Prototype Development
`
`Personalis Genome
`Services
`
`Feasibility
`
`Disease Variant
`Discovery Service
`
`v1 Development
`
`Exome Plus
`
`Moyamoya Proj
`
`Spec & Resource
`
`v1 Testing
`
`AGBT
`
`VA Proj
`
`Prototype Dev
`
`Prototype Test
`
`v1 Dev
`
`Personalis EX2100
`
`
`
`Content Development Updates
`
`• Newly granted access to large public sequencing projects including
`– UK10K : 4000 genomes, 6000 exomes
`• > $16 M investment from Wellcome Trust 2010
`• > 4,000 whole genomes in healthy individuals
`• > 6,000 exomes in disease areas such as neurodevelopment, obesity, rare diseases
`– NHLBI GO Exome Sequencing Project: ~500 exomes: Heart, Lung, Blood Dz
`– 1000 Genomes (exomes)
`– Personal Genomes Project (whole genomes)
`– dbGAP data – Kabuki syndrome, Miller syndrome exomes
`– Represents > 2.5 PB of data in total and > $20M in research grants to date
`
`• May be a cost-effective way to build our library of genomes that enable
`us to
`– Establish population allele frequencies to enable filtering of disease causing var
`– Provide potential control sets when customers don’t have controls for comparison
`– Establish normal ranges for genomes for quality control purposes
`– Validate our pipeline and algorithms
`
`Personalis EX2100
`
`
`
`MendelDB Dashboard
`
`•
`
`•
`
`•
`
`High quality curated DB of Mendelian
`phenotypes and their variants
`– Managed by Sarah Garcia and
`Gemma Chandratillake, both
`Genetics Ph.D. & Genetic Counselors
`
`Critical content to support Disease
`Variant Discovery Service and Genome
`Interpretation Service
`
`Finished (~560) GeneReviews > 600
`common Mendelian disease phenotypes
`
`• Will then continue phenotype curation
`and variant curation from other sources
`
`•
`
`Flexible workforce for other curation
`tasks in the future
`
`# phenotypes
`
`# genes (blue)
`# variants (red)
`
`productivity
`(rows/hr)
`
`Personalis EX2100
`
`
`
`VarimedDB Dashboard
`
`687,432 relationships
`
`254,306 variants
`
`300,000
`
`250,000
`
`200,000
`
`150,000
`
`100,000
`
`50,000
`
`0
`
`Numbre of distinct variants
`
`9/27/2012
`8/27/2012
`7/27/2012
`6/27/2012
`5/27/2012
`4/27/2012
`3/27/2012
`2/27/2012
`1/27/2012
`12/27/2011
`11/27/2011
`10/27/2011
`9/27/2011
`8/27/2011
`7/27/2011
`6/27/2011
`5/27/2011
`4/27/2011
`3/27/2011
`2/27/2011
`1/27/2011
`12/27/2010
`11/27/2010
`10/27/2010
`9/27/2010
`8/27/2010
`7/27/2010
`6/27/2010
`5/27/2010
`4/27/2010
`3/27/2010
`2/27/2010
`1/27/2010
`
`9/27/2012
`8/27/2012
`7/27/2012
`6/27/2012
`5/27/2012
`4/27/2012
`3/27/2012
`2/27/2012
`1/27/2012
`12/27/2011
`11/27/2011
`10/27/2011
`9/27/2011
`8/27/2011
`7/27/2011
`6/27/2011
`5/27/2011
`4/27/2011
`3/27/2011
`2/27/2011
`1/27/2011
`12/27/2010
`11/27/2010
`10/27/2010
`9/27/2010
`8/27/2010
`7/27/2010
`6/27/2010
`5/27/2010
`4/27/2010
`3/27/2010
`2/27/2010
`1/27/2010
`
`Date
`
`12,981 papers
`
`14,500
`
`12,500
`
`10,500
`
`8,500
`
`6,500
`
`4,500
`
`2,500
`
`Numbre of papers
`
`Date
`
`5,284 phenotypes
`
`800,000
`
`700,000
`
`600,000
`
`500,000
`
`400,000
`
`300,000
`
`200,000
`
`100,000
`
`0
`
`Number of rows
`
`6,000
`
`5,000
`
`4,000
`
`3,000
`
`2,000
`
`1,000
`
`0
`
`Numbre of phenotypes
`
`9/27/2012
`
`7/27/2012
`
`5/27/2012
`
`3/27/2012
`
`1/27/2012
`
`11/27/2011
`
`9/27/2011
`
`7/27/2011
`
`5/27/2011
`
`3/27/2011
`
`1/27/2011
`
`11/27/2010
`
`9/27/2010
`
`7/27/2010
`
`5/27/2010
`
`3/27/2010
`
`1/27/2010
`
`9/27/2012
`8/27/2012
`7/27/2012
`6/27/2012
`5/27/2012
`4/27/2012
`3/27/2012
`2/27/2012
`1/27/2012
`12/27/2011
`11/27/2011
`10/27/2011
`9/27/2011
`8/27/2011
`7/27/2011
`6/27/2011
`5/27/2011
`4/27/2011
`3/27/2011
`2/27/2011
`1/27/2011
`12/27/2010
`11/27/2010
`10/27/2010
`9/27/2010
`8/27/2010
`7/27/2010
`6/27/2010
`5/27/2010
`4/27/2010
`3/27/2010
`2/27/2010
`1/27/2010
`
`Date
`
`Date
`
`Personalis EX2100
`
`
`
`Scientific Computing Infrastructure
`
`• Hiring is a key challenge:
`– Director of High Performance Computing and Architecture
`– Linux Systems Admin
`
`• Doing a reassessment of scientific computing needs (storage, CPUs)
`for next 6 months because of recent (good) developments:
`– Ops: VA project (processing >300 genomes every 2 months)
`– Ops: Moyamoya and customer projects
`– R&D: Access to very large public genome/exome databases (as discussed
`earlier)
`– R&D: General R&D needs
`
`• Near Term Needs
`– Additional 107 TB of storage for Hitachi HNAS
`– Backup solution ordered (disk to disk, and disk to tape)
`
`Personalis EX2100
`
`
`
`Scientific Computing Infrastructure
`
`Personalis EX2100
`
`
`
`Hiring Update
`
`• A member our R&D team has been on medical leave for nearly 2 months
`• New Hires have enabled us to reach our target staffing in the pipeline & apps
`groups
`Anil Patwardhan, Ph.D.: Sr Bioinformatics Scientist
`•
`Steve Chervitz, Ph.D.: Sr Bioinformatics Scientist
`•
`• Ming Li, Ph.D.: Sr Software Lead (Test and Build Engineer)
`Jing Wang, Ph,D: BI Engineer
`•
`• Open Positions
`Director of High Performance Computing and Architecture
`•
`Linux systems admin
`•
`
`Pipeline Mgr
`
`(Lam)
`
`BI Pipeline
`Engineer
`
`(Newburge)
`
`BI Pipeline
`Engineer
`
`(Wang)
`
`Test/Build
`Engineer
`(Ming Li)
`
`BI Analyst
`
`(Bartha)
`
`R&D (Chen)
`
`Director
`Accuracy
`R&D
`
`(Pratt)
`
`BI Tools
`(Harris)
`
`Mol Bio/Lab
`
`(Luo)
`
`BI App
`Scientist
`
`(Clark)
`
`BI Apps &
`Research
`Mgr
`
`(Chen)
`
`BI App
`Engineer
`(Patwardhan
`)
`
`Original Team
`
`New hires (started)
`
`Scientific
`Content &
`Curation
`Mgr
`
`Sr Project
`Mgr
`
`(Kirk)
`
`BI Scientist
`(Chervitz)
`
`Genomics
`Counselor
`
`(Chandratilla
`ke)
`
`Genomics
`Counselor
`
`(Garcia)
`
`5 Part Time
`Curation
`Scientists
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`Personalis EX2100
`
`
`
`Summary of Resource Allocation
`
`Accuracy R&D
`Mark Pratt
`Gabor Barth
`Jason Harris
`Shujun Luo
`
`Pipeline R&D
`Hugo Lam
`Daniel Newburger
`Ming Li
`Jing Wang
`
`Apps R&D
`Rong Chen
`Michael Clark
`Anil Padawardhan
`Steve Chervitz
`
`Content R&D
`Sarah Garcia
`Gemma Chandratillake
`PT Curators
`
`Personalis
`Genome
`Services
`
`Disease Variant
`Discovery
`Service
`
`Customer
`Projects
`
`Research
`Projects
`
`Ethics Board
`
`Personalis EX2100
`
`
`
`AMP Conference
`Takeaways Regarding Reimbursement of Clinical Dx
`
`• Annual conference attended by molecular pathologists
`• CPT coding changes to reduce code stacking for genetic tests
`• Key Private payer reimbursement criteria
`• Lee N. Newcomer, MD, MHA, SVP, UnitedHealthcare
`• Analytic validity
`• Clinical validity
`• Clinical utility
`• Medicare reimbursement excludes
`• Screening if no signs/symptoms
`• Risk assessment for patient or family member if no signs/symptoms
`• Diagnoses that are not actionable
`Implications for our clinical dx strategy
`• Focus on clinical dx asso with specific diseases/disease categories that are actionable
`(e.g. cardiomyopathy panels, heritable cancer, etc) and/or currently reimbursed will
`maximize chances of reimbursement. Focused interpretation on disease panels reflexing
`to whole exome or genome may be a way to do this.
`• Healthy people genetic screening (GIS) will have a harder time getting reimbursement in
`the short to medium term
`
`•
`
`Personalis EX2100
`
`
`
`Risk
`
`• Aggressive timeline
`
`• Pipeline performance risk
`
`• Product Differentiation
`
`Risks and Mitigation
`
`Mitigation
`
`• Minimized “research” features that could result in product
`delay, focused on achievable, differentiated features for v1
`
`• Approximately 2 days to run 1 whole genome currently on a 40
`core machine
`• Prioritizing performance optimization, goal to reduce by 50%
`• Assess how we can address with more hardware, cloud
`
`• Prioritized differentiation in three key product areas: Exome+ ,
`SV’s, accuracy/quality, content, visualization
`• Giving conference talks at AGBT to discuss differentiation
`
`• Exome plus costs, may limit margins on product
`
`• Actively working on cost model and ways to reduce cost
`
`• New sequencing platforms antiquate our
`accuracy gains
`
`• Obtain data from orthogonal seq platforms and integrate as
`appropriate
`
`• Hiring of Unix sys admin and director of high
`performance computing.
`
`• Redoubled efforts with in-house recruiter to identify more
`leads
`
`• Long lead time content curation and content
`quality items for GIS and DVDS
`
`• Started dev on those items with long lead times to develop
`concurrently with Pipeline (MendelDB, etc)
`
`• Licensing of applications and content for analysis
`
`• Ethical use of Genomes for R&D
`
`• Systematically reviewing and applying for licenses for key
`content and algorithms
`
`• Ethics board approval for all Genomes used for R&D
`• Part of orientation training
`
`Personalis EX2100
`
`
`
`Next Steps & Priorities
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`Continue development on PGS v1 priorities with goal of Feb 2013 launch at AGBT
`
`Execute on product features required for VA project, enable success
`
`Start implementing DVDS workflow and exploring early collaborations
`
`Continue Hiring for open scientific computing positions
`
`Continue to execute on content priorities, develop longer term content strategy
`
`Continue to work with OPS team to deliver successes with early customers and
`collaborators
`
`Personalis EX2100
`
`
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