SlideShare une entreprise Scribd logo
1  sur  20
AssureRx Health, Inc.   CONFIDENTIAL   1
Mayo Clinic and Cincinnati Children’s Hospital
                       experience & technology

                                    • Mayo: Patent-pending technology
                                    • >5,000 patients genotyped
                                    • “Gene Team” expertise
                                    • Routine in clinical use



• CCH: Patent-pending
technology
• >7,000 patients genotyped
• Standard-of-care
• Genetic and non-genetic factors
• Drug-drug interactions


 Privately-held with key investments from Claremont Creek
 Ventures, Sequoia Capital ventures, CincyTech and other investment
 groups.
AssureRx Health, Inc.   CONFIDENTIAL   3
Lifetime prevalence of psychiatric illnesses


      Eating Disorders             1-3%

                PTSD                3.5%

                ADHD                       4.1 %

       Mood Disorders                                      9.5%

     Anxiety Disorders                                                        15%

           Cancer (All)               3.7%

Coronary Heart Disease                             5.6%

             Diabetes                                     8%

                          0            5                  10              1         20
                                                                          5
                                            Percentage of US Population

        Two-fold greater aggregate prevalence of psychiatric illness vs
        cancer, cardiovascular, or metabolic disorders (NIMH, 2009; Am. Cancer
        Society 2006; Am. Diabetes Assn, 2008; Am. Heart Assn, 2006, Lindner Center of
        Hope, Cincinnati, OH).
CYP450 Metabolizer Phenotypes



ULTRA-RAPID: Increased expression of a metabolizing
enzyme, and will metabolize a drug at a rapid rate.


EXTENSIVE: Wild type or “normal” phenotype,
in some cases.


INTERMEDIATE: An individual who possesses one semi-
functional or non-functional allele


POOR: An individual with decreased or no expression
of a metabolizing enzyme, and metabolize a drug very
slowly or not at all.
19 Antidepressants in a
                         Pharmacogenomic support algorithm

                                                    5HT2A Antagonist/SSRI (SARI)
Selective Serotonin Reuptake Blockers (SSRI)
                                                    Nefazodone (Serzone®)
Citalopram (Celexa®)
                                                    Trazodone (Desyrel®)
Fluoxetine (Prozac®)
                                                    Trazodone ER (Oleptro®)
Escitalopram (Lexapro®)
Fluvoxamine (Luvox®)
                                                    Tricyclic (TCA)
Paroxetine (Paxil®)
                                                    Imipramine (Tofranil®)
Sertraline (Zoloft®)
                                                    Desipramine (Norpramin®)
                                                    Amitriptyline (Evavil®)
SSRI/5HT-1A partial agonist
                                                    Nortriptyline (Pamelor®)
Vilazadone (Viibryd®)
                                                    Clomipramine (Anafranil ®)
Aripiprazole (Abilify®) (D2/1A partial agonist)
                                                    Doxepin (Sinequan®)
                                                    Protriptyline (Vivactil®)
Norepineprhine-Dopamine Reuptake Blockers (NDRI)
                                                    Trimipramine (Surmontil®)
Bupropion (& SR, XL (Wellbutrin® or Zyban®)
Bupropion Hydrobromide (Aplenzin®)
                                                    Tetracyclic
                                                    Maprotiline (Ludiomil®)
Serotonin-Norepineprhine Reuptake Blockers (SNRI)
                                                    Amoxapine (Asendin®)
Venlafaxine (Effexor XR®)
Desvenlafaxine (Pristiq®)
                                                    Irreversible MAO-A/B Inhbitors
Duloxetine (Cymbalta®)
                                                    Isocarboxazid (Marplan®)
                                                    Phenelzine (Nardil®)
Noradrenergic/Specific Serotonergic (NaSSA)
                                                    Tranylcypromine (Parnate®)
Mirtazepine (Remeron®)
                                                    Selegiline (Emsam® patch; MAOB)
Using the GeneSightRx® treatment-support
                             solution for medication selection

e-Test ordered
                                                    Web-based patient report




                        Proprietary
                        Algorithm



PGx Sample


                 Clinical Laboratory Improvement
                 Amendments (CLIA) compliant

                 College of American Pathologists
                 (CAP) accredited

                 Certified by the New York
                 Department of Health
GeneSightRx® Psychotropic Test

Genotype              Phenotype           Interpretive Drug         Medication
                                               Sorting               Binning



CYP2D6            Metabolizer Status                                     Use as
                                                                        Directed
CYP2C19           Metabolizer Status

CYP2C9            Metabolizer Status        Effect of
                                           Composite
                                                                        Use with
                                          Phenotype on
CYP1A2            Metabolizer Status                                    Caution
                                           Each Drug

SLC6A4            Transporter Activity
                                                                 Use with Caution and
5HTR2A             Receptor Activity                                More Frequent
                                                                      Monitoring


 1.   The patient’s genotype is determined for each gene in the panel
 2.   A phenotype is predicted for each genotype
 3.   A composite phenotype for each drug is created based on all 6
      phenotypes
 4.   The 19 most commonly prescribed antidepressants and 13
      antipsychotics are positioned in a green, yellow, or red “bin”.
Sample Patient Report
GeneSightRx Psychotropics
Meta-analysis: GeneSightRx
                  improves 8 week antidepressant response




A meta-analysis of 3 independent, prospective, controlled studies of GeneSightRx-
managed patients shows a 28% reduction in the rate of failure among patients who
had previously failed pharmacotherapy for MDD.
Cost benefits of improving therapeutic response
                     with GeneSightRx®


       Direct medical costs and productivity costs
                                             Fail to
Annual MDD costs per patient                           Respond
                                          respond
Annual direct medical costs per patient     $12,155      $5,755
 Pharmacy - Depression drug costs            $1,246        $429
 Inpatient                                  $2,600       $1,283
 Outpatient Physician                       $6,053        $1,913
 Other                                      $2,256       $2,130
Employer productivity costs                 $4,973       $1,015
 Productivity                                 $504         $278
 Absenteeism                                $4,469         $737

Annual medical & productivity cost/pt      $17,128      $6,770

Comparisons of TAU and GeneSightRx            TAU         GSRx
Failure to respond rate                        79%          51%
Response rate                                  21%         47%
Conclusions

Prospective, randomized double-blind clinical trials show that
GeneSightRx® improves antidepressant efficacy compared to
patients who receive treatment as usual (TAU).

Efficacy improvement is greatest for patients on multiple
medications (likely to be treatment-resistant), and those
identified by the test to be taking problematic, red-binned
drugs (data not shown).

GeneSightRx® is a rapid and effective pharmacogenomic
decision support tool, and can be used for cohort stratification
prior to clinical trials.
AssureRx Health, Inc.   CONFIDENTIAL   13
Demogenics of 17,131 human genome sequences




AssureRx Health, Inc.                                     CONFIDENTIAL   14
How do we process all of these sequences?
Data production   Data storage, manipulation   Data annotation, interpretation




                                                   Report generation
AssureRx Health, Inc.   CONFIDENTIAL   16
Lee Hood, IOM February 27, 2012
Trends in NGS and Drug Development

1. Precompetitive data sharing using collaborative informatics:
    • tranSMART
    • TransCelerate BioPharma


2. Nanopore-based, single molecule sequencing.


1. Improved understanding of human variation of all types–
    “it isn't just the SNPs anymore.”




AssureRx Health, Inc.                                CONFIDENTIAL   18
Applications in Drug Discovery
“The ideal nucleic acid sequencing technology for drug discovery
and development should:
• Sequence natural DNA/RNA fragments of various sizes fully with
  minimal (or no) errors
• Haplotype phasing on a chromosome scale;
• Generate no sequence-dependent or other biases;
• Require minimum quantities of input material, ideally single cells;
• Have high/complete efficiency in all of the sequencing steps;
• Detect modified nucleotides (such as methylated cytosines)
  directly;
• Operate in laboratories and low-resource settings without special
  external environment requirements such as temperature and
  humidity control.” – Mike Braxenthaler, Roche and Pistoia Alliance

 AssureRx Health, Inc.                                 CONFIDENTIAL   19
The Biggest Problem we can’t solve




                               Potential for Drug-Drug Interactions!
                            Number of Patients Aged 18-24 / VA Med. Ctr.
                           Average number of prescription drugs per day
                        3,125        5,860        6,001          12, 392
                        average      average      average        average
                        number of    number of    number of      number of
                        drugs each   drugs each   drugs each     drugs each
                        day =19      day = 15     day = 12       day = 7

AssureRx Health, Inc.                                          CONFIDENTIAL   20

Contenu connexe

Tendances

Addex Jan 2010 Presentation
Addex Jan 2010 PresentationAddex Jan 2010 Presentation
Addex Jan 2010 Presentationguestff90766
 
7 neelapu
7 neelapu7 neelapu
7 neelapuspa718
 
Vienna practical experience 2007
Vienna practical experience 2007Vienna practical experience 2007
Vienna practical experience 2007aaaasong
 
1 s2.0-s0378874113003917-main
1 s2.0-s0378874113003917-main1 s2.0-s0378874113003917-main
1 s2.0-s0378874113003917-mainNikole Villalobos
 
Erectile Dysfunction Help
Erectile Dysfunction HelpErectile Dysfunction Help
Erectile Dysfunction Helpedhelp
 
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticals
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticalsErlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticals
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticalsTaj Pharma
 
Pharmacogenetics and drug response
Pharmacogenetics and drug responsePharmacogenetics and drug response
Pharmacogenetics and drug responseMaizbha Uddin Ahmed
 
Epilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyEpilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyDr. Siddhartha Dutta
 
Gleevec group presentation#1
Gleevec group presentation#1Gleevec group presentation#1
Gleevec group presentation#1erussell10
 
Erlotinib Tablet USP Taj Pharma SmPC
Erlotinib Tablet USP Taj Pharma SmPCErlotinib Tablet USP Taj Pharma SmPC
Erlotinib Tablet USP Taj Pharma SmPCTajPharmaQC
 
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...Taj Pharma
 
Prescribing in physiological conditions
Prescribing in physiological conditionsPrescribing in physiological conditions
Prescribing in physiological conditionsDr. Siddhartha Dutta
 
Pemetrexed for Injection Taj Pharma SmPC
Pemetrexed for Injection Taj Pharma SmPCPemetrexed for Injection Taj Pharma SmPC
Pemetrexed for Injection Taj Pharma SmPCTajPharmaQC
 
Pharmacogenetics
PharmacogeneticsPharmacogenetics
PharmacogeneticsLarry Baum
 
Daptomycin for Injection Taj Pharma SmPC
Daptomycin for Injection Taj Pharma SmPCDaptomycin for Injection Taj Pharma SmPC
Daptomycin for Injection Taj Pharma SmPCTajPharmaQC
 
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96Ali Obergrussberger
 
Escitalopram Tablets Taj Pharma SmPC
Escitalopram Tablets Taj Pharma SmPCEscitalopram Tablets Taj Pharma SmPC
Escitalopram Tablets Taj Pharma SmPCTajPharmaQC
 

Tendances (20)

asdads
asdadsasdads
asdads
 
Newest Strategies in the Treatment of CML/CLL
Newest Strategies in the Treatment of CML/CLLNewest Strategies in the Treatment of CML/CLL
Newest Strategies in the Treatment of CML/CLL
 
Addex Jan 2010 Presentation
Addex Jan 2010 PresentationAddex Jan 2010 Presentation
Addex Jan 2010 Presentation
 
7 neelapu
7 neelapu7 neelapu
7 neelapu
 
Vienna practical experience 2007
Vienna practical experience 2007Vienna practical experience 2007
Vienna practical experience 2007
 
1 s2.0-s0378874113003917-main
1 s2.0-s0378874113003917-main1 s2.0-s0378874113003917-main
1 s2.0-s0378874113003917-main
 
Erectile Dysfunction Help
Erectile Dysfunction HelpErectile Dysfunction Help
Erectile Dysfunction Help
 
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticals
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticalsErlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticals
Erlotinib 100 mg, 150mg film coated tablets smpc- taj pharmaceuticals
 
Demenza
DemenzaDemenza
Demenza
 
Pharmacogenetics and drug response
Pharmacogenetics and drug responsePharmacogenetics and drug response
Pharmacogenetics and drug response
 
Epilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyEpilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapy
 
Gleevec group presentation#1
Gleevec group presentation#1Gleevec group presentation#1
Gleevec group presentation#1
 
Erlotinib Tablet USP Taj Pharma SmPC
Erlotinib Tablet USP Taj Pharma SmPCErlotinib Tablet USP Taj Pharma SmPC
Erlotinib Tablet USP Taj Pharma SmPC
 
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...
Pemetrexed 100mg and 500mg powder for concentrate for solution for infusion s...
 
Prescribing in physiological conditions
Prescribing in physiological conditionsPrescribing in physiological conditions
Prescribing in physiological conditions
 
Pemetrexed for Injection Taj Pharma SmPC
Pemetrexed for Injection Taj Pharma SmPCPemetrexed for Injection Taj Pharma SmPC
Pemetrexed for Injection Taj Pharma SmPC
 
Pharmacogenetics
PharmacogeneticsPharmacogenetics
Pharmacogenetics
 
Daptomycin for Injection Taj Pharma SmPC
Daptomycin for Injection Taj Pharma SmPCDaptomycin for Injection Taj Pharma SmPC
Daptomycin for Injection Taj Pharma SmPC
 
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96
Impedance and EFP recordings of iCell Cardiomyocytes2 on the CardioExcyte 96
 
Escitalopram Tablets Taj Pharma SmPC
Escitalopram Tablets Taj Pharma SmPCEscitalopram Tablets Taj Pharma SmPC
Escitalopram Tablets Taj Pharma SmPC
 

En vedette

Encuentro Empresarios SCD_ Experiencia Clientes
Encuentro Empresarios SCD_ Experiencia ClientesEncuentro Empresarios SCD_ Experiencia Clientes
Encuentro Empresarios SCD_ Experiencia ClientesCustomerTrigger
 
Requirements - Overweight or Anorexia?
Requirements - Overweight or Anorexia?Requirements - Overweight or Anorexia?
Requirements - Overweight or Anorexia?Mike Eckersley
 
Fist Signs Of Spring Waterville, Me.
Fist Signs Of Spring   Waterville, Me.Fist Signs Of Spring   Waterville, Me.
Fist Signs Of Spring Waterville, Me.Ramon A. de Mier
 
What's New in Puppet Enterprise 2015.3
What's New in Puppet Enterprise 2015.3What's New in Puppet Enterprise 2015.3
What's New in Puppet Enterprise 2015.3Puppet
 
3 ways to improve searchability
3 ways to improve searchability3 ways to improve searchability
3 ways to improve searchabilityTheresa Putkey
 
Sabins Residence
Sabins ResidenceSabins Residence
Sabins Residencelampertaia
 
Tecnologias de la Comunicación y la Información (TICs)
Tecnologias de la Comunicación y la Información (TICs)Tecnologias de la Comunicación y la Información (TICs)
Tecnologias de la Comunicación y la Información (TICs)Dominig Yair Brayan Walker
 
pi life sciences consultancy
pi life sciences consultancypi life sciences consultancy
pi life sciences consultancypi
 
Tutorial para alumnos
Tutorial para alumnosTutorial para alumnos
Tutorial para alumnosIES LLANERA
 
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...devopsdaysaustin
 
Furniture hire or rental for events & exhibitions including chair hire, table...
Furniture hire or rental for events & exhibitions including chair hire, table...Furniture hire or rental for events & exhibitions including chair hire, table...
Furniture hire or rental for events & exhibitions including chair hire, table...exhibithire
 
Apresentação para décimo segundo ano de 2016 7, aula 84-85
Apresentação para décimo segundo ano de 2016 7, aula 84-85Apresentação para décimo segundo ano de 2016 7, aula 84-85
Apresentação para décimo segundo ano de 2016 7, aula 84-85luisprista
 
Apresentação para décimo segundo ano de 2016 7, aula 92-93
Apresentação para décimo segundo ano de 2016 7, aula 92-93Apresentação para décimo segundo ano de 2016 7, aula 92-93
Apresentação para décimo segundo ano de 2016 7, aula 92-93luisprista
 
Taller de Oportunidades de Negocio
Taller de Oportunidades de NegocioTaller de Oportunidades de Negocio
Taller de Oportunidades de NegocioMaria Torres
 

En vedette (16)

Actividad 4
Actividad 4Actividad 4
Actividad 4
 
Encuentro Empresarios SCD_ Experiencia Clientes
Encuentro Empresarios SCD_ Experiencia ClientesEncuentro Empresarios SCD_ Experiencia Clientes
Encuentro Empresarios SCD_ Experiencia Clientes
 
Requirements - Overweight or Anorexia?
Requirements - Overweight or Anorexia?Requirements - Overweight or Anorexia?
Requirements - Overweight or Anorexia?
 
Fist Signs Of Spring Waterville, Me.
Fist Signs Of Spring   Waterville, Me.Fist Signs Of Spring   Waterville, Me.
Fist Signs Of Spring Waterville, Me.
 
What's New in Puppet Enterprise 2015.3
What's New in Puppet Enterprise 2015.3What's New in Puppet Enterprise 2015.3
What's New in Puppet Enterprise 2015.3
 
3 ways to improve searchability
3 ways to improve searchability3 ways to improve searchability
3 ways to improve searchability
 
Sabins Residence
Sabins ResidenceSabins Residence
Sabins Residence
 
Tecnologias de la Comunicación y la Información (TICs)
Tecnologias de la Comunicación y la Información (TICs)Tecnologias de la Comunicación y la Información (TICs)
Tecnologias de la Comunicación y la Información (TICs)
 
pi life sciences consultancy
pi life sciences consultancypi life sciences consultancy
pi life sciences consultancy
 
Tutorial para alumnos
Tutorial para alumnosTutorial para alumnos
Tutorial para alumnos
 
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...
2016 - IGNITE - Being an introvert and at a conference, not as hellish as you...
 
Furniture hire or rental for events & exhibitions including chair hire, table...
Furniture hire or rental for events & exhibitions including chair hire, table...Furniture hire or rental for events & exhibitions including chair hire, table...
Furniture hire or rental for events & exhibitions including chair hire, table...
 
RCPA
RCPARCPA
RCPA
 
Apresentação para décimo segundo ano de 2016 7, aula 84-85
Apresentação para décimo segundo ano de 2016 7, aula 84-85Apresentação para décimo segundo ano de 2016 7, aula 84-85
Apresentação para décimo segundo ano de 2016 7, aula 84-85
 
Apresentação para décimo segundo ano de 2016 7, aula 92-93
Apresentação para décimo segundo ano de 2016 7, aula 92-93Apresentação para décimo segundo ano de 2016 7, aula 92-93
Apresentação para décimo segundo ano de 2016 7, aula 92-93
 
Taller de Oportunidades de Negocio
Taller de Oportunidades de NegocioTaller de Oportunidades de Negocio
Taller de Oportunidades de Negocio
 

Similaire à Sf Genome Data Analysis Meeting Final R

Psychopharmacogenetics
PsychopharmacogeneticsPsychopharmacogenetics
Psychopharmacogeneticsswanandpathak
 
Side Effects Management for the Ovarian Cancer Community
Side Effects Management for the Ovarian Cancer CommunitySide Effects Management for the Ovarian Cancer Community
Side Effects Management for the Ovarian Cancer Communitybkling
 
Current Epilepsy Treatment Options
Current Epilepsy Treatment OptionsCurrent Epilepsy Treatment Options
Current Epilepsy Treatment OptionsEFEPA
 
20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized Medicine20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized MedicineMichel Dumontier
 
Pharmacogenetics devang
Pharmacogenetics devangPharmacogenetics devang
Pharmacogenetics devangDevang Parikh
 
pharmacogenomics-171011132627.pptx
pharmacogenomics-171011132627.pptxpharmacogenomics-171011132627.pptx
pharmacogenomics-171011132627.pptxAnandKumar279666
 
Advancement in anti-depression drugs
Advancement in anti-depression drugsAdvancement in anti-depression drugs
Advancement in anti-depression drugsDiwyanshi Zinzuvadia
 
Prolactinoma
ProlactinomaProlactinoma
Prolactinomamssa_500
 
Intravenous anti epileptic drug review
Intravenous anti epileptic drug reviewIntravenous anti epileptic drug review
Intravenous anti epileptic drug reviewYung-Tsai Chu
 
AIM Example Report
AIM Example ReportAIM Example Report
AIM Example ReportTony Fanelli
 
Antidepressants /certified fixed orthodontic courses by Indian dental academy
Antidepressants  /certified fixed orthodontic courses by Indian dental academy Antidepressants  /certified fixed orthodontic courses by Indian dental academy
Antidepressants /certified fixed orthodontic courses by Indian dental academy Indian dental academy
 

Similaire à Sf Genome Data Analysis Meeting Final R (20)

Psychopharmacogenetics
PsychopharmacogeneticsPsychopharmacogenetics
Psychopharmacogenetics
 
Side Effects Management for the Ovarian Cancer Community
Side Effects Management for the Ovarian Cancer CommunitySide Effects Management for the Ovarian Cancer Community
Side Effects Management for the Ovarian Cancer Community
 
Current Epilepsy Treatment Options
Current Epilepsy Treatment OptionsCurrent Epilepsy Treatment Options
Current Epilepsy Treatment Options
 
Presentasi farmakogenomik
Presentasi farmakogenomikPresentasi farmakogenomik
Presentasi farmakogenomik
 
20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized Medicine20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized Medicine
 
Pharmacogenetics devang
Pharmacogenetics devangPharmacogenetics devang
Pharmacogenetics devang
 
Pharmacogenomics
PharmacogenomicsPharmacogenomics
Pharmacogenomics
 
pharmacogenomics-171011132627.pptx
pharmacogenomics-171011132627.pptxpharmacogenomics-171011132627.pptx
pharmacogenomics-171011132627.pptx
 
Advancement in anti-depression drugs
Advancement in anti-depression drugsAdvancement in anti-depression drugs
Advancement in anti-depression drugs
 
Pharmacogenomics
PharmacogenomicsPharmacogenomics
Pharmacogenomics
 
cocogenetics.pdf
cocogenetics.pdfcocogenetics.pdf
cocogenetics.pdf
 
Pharmacogenetics
PharmacogeneticsPharmacogenetics
Pharmacogenetics
 
Prolactinoma
ProlactinomaProlactinoma
Prolactinoma
 
Intravenous anti epileptic drug review
Intravenous anti epileptic drug reviewIntravenous anti epileptic drug review
Intravenous anti epileptic drug review
 
AIM Example Report
AIM Example ReportAIM Example Report
AIM Example Report
 
Antidepressants /certified fixed orthodontic courses by Indian dental academy
Antidepressants  /certified fixed orthodontic courses by Indian dental academy Antidepressants  /certified fixed orthodontic courses by Indian dental academy
Antidepressants /certified fixed orthodontic courses by Indian dental academy
 
Pharmacogenomics
PharmacogenomicsPharmacogenomics
Pharmacogenomics
 
TDM of ARV drugs
 TDM of ARV drugs TDM of ARV drugs
TDM of ARV drugs
 
phants
phantsphants
phants
 
Epilepsy
EpilepsyEpilepsy
Epilepsy
 

Sf Genome Data Analysis Meeting Final R

  • 1. AssureRx Health, Inc. CONFIDENTIAL 1
  • 2. Mayo Clinic and Cincinnati Children’s Hospital experience & technology • Mayo: Patent-pending technology • >5,000 patients genotyped • “Gene Team” expertise • Routine in clinical use • CCH: Patent-pending technology • >7,000 patients genotyped • Standard-of-care • Genetic and non-genetic factors • Drug-drug interactions Privately-held with key investments from Claremont Creek Ventures, Sequoia Capital ventures, CincyTech and other investment groups.
  • 3. AssureRx Health, Inc. CONFIDENTIAL 3
  • 4. Lifetime prevalence of psychiatric illnesses Eating Disorders 1-3% PTSD 3.5% ADHD 4.1 % Mood Disorders 9.5% Anxiety Disorders 15% Cancer (All) 3.7% Coronary Heart Disease 5.6% Diabetes 8% 0 5 10 1 20 5 Percentage of US Population Two-fold greater aggregate prevalence of psychiatric illness vs cancer, cardiovascular, or metabolic disorders (NIMH, 2009; Am. Cancer Society 2006; Am. Diabetes Assn, 2008; Am. Heart Assn, 2006, Lindner Center of Hope, Cincinnati, OH).
  • 5. CYP450 Metabolizer Phenotypes ULTRA-RAPID: Increased expression of a metabolizing enzyme, and will metabolize a drug at a rapid rate. EXTENSIVE: Wild type or “normal” phenotype, in some cases. INTERMEDIATE: An individual who possesses one semi- functional or non-functional allele POOR: An individual with decreased or no expression of a metabolizing enzyme, and metabolize a drug very slowly or not at all.
  • 6. 19 Antidepressants in a Pharmacogenomic support algorithm 5HT2A Antagonist/SSRI (SARI) Selective Serotonin Reuptake Blockers (SSRI) Nefazodone (Serzone®) Citalopram (Celexa®) Trazodone (Desyrel®) Fluoxetine (Prozac®) Trazodone ER (Oleptro®) Escitalopram (Lexapro®) Fluvoxamine (Luvox®) Tricyclic (TCA) Paroxetine (Paxil®) Imipramine (Tofranil®) Sertraline (Zoloft®) Desipramine (Norpramin®) Amitriptyline (Evavil®) SSRI/5HT-1A partial agonist Nortriptyline (Pamelor®) Vilazadone (Viibryd®) Clomipramine (Anafranil ®) Aripiprazole (Abilify®) (D2/1A partial agonist) Doxepin (Sinequan®) Protriptyline (Vivactil®) Norepineprhine-Dopamine Reuptake Blockers (NDRI) Trimipramine (Surmontil®) Bupropion (& SR, XL (Wellbutrin® or Zyban®) Bupropion Hydrobromide (Aplenzin®) Tetracyclic Maprotiline (Ludiomil®) Serotonin-Norepineprhine Reuptake Blockers (SNRI) Amoxapine (Asendin®) Venlafaxine (Effexor XR®) Desvenlafaxine (Pristiq®) Irreversible MAO-A/B Inhbitors Duloxetine (Cymbalta®) Isocarboxazid (Marplan®) Phenelzine (Nardil®) Noradrenergic/Specific Serotonergic (NaSSA) Tranylcypromine (Parnate®) Mirtazepine (Remeron®) Selegiline (Emsam® patch; MAOB)
  • 7. Using the GeneSightRx® treatment-support solution for medication selection e-Test ordered Web-based patient report Proprietary Algorithm PGx Sample Clinical Laboratory Improvement Amendments (CLIA) compliant College of American Pathologists (CAP) accredited Certified by the New York Department of Health
  • 8. GeneSightRx® Psychotropic Test Genotype Phenotype Interpretive Drug Medication Sorting Binning CYP2D6 Metabolizer Status Use as Directed CYP2C19 Metabolizer Status CYP2C9 Metabolizer Status Effect of Composite Use with Phenotype on CYP1A2 Metabolizer Status Caution Each Drug SLC6A4 Transporter Activity Use with Caution and 5HTR2A Receptor Activity More Frequent Monitoring 1. The patient’s genotype is determined for each gene in the panel 2. A phenotype is predicted for each genotype 3. A composite phenotype for each drug is created based on all 6 phenotypes 4. The 19 most commonly prescribed antidepressants and 13 antipsychotics are positioned in a green, yellow, or red “bin”.
  • 10. Meta-analysis: GeneSightRx improves 8 week antidepressant response A meta-analysis of 3 independent, prospective, controlled studies of GeneSightRx- managed patients shows a 28% reduction in the rate of failure among patients who had previously failed pharmacotherapy for MDD.
  • 11. Cost benefits of improving therapeutic response with GeneSightRx® Direct medical costs and productivity costs Fail to Annual MDD costs per patient Respond respond Annual direct medical costs per patient $12,155 $5,755 Pharmacy - Depression drug costs $1,246 $429 Inpatient $2,600 $1,283 Outpatient Physician $6,053 $1,913 Other $2,256 $2,130 Employer productivity costs $4,973 $1,015 Productivity $504 $278 Absenteeism $4,469 $737 Annual medical & productivity cost/pt $17,128 $6,770 Comparisons of TAU and GeneSightRx TAU GSRx Failure to respond rate 79% 51% Response rate 21% 47%
  • 12. Conclusions Prospective, randomized double-blind clinical trials show that GeneSightRx® improves antidepressant efficacy compared to patients who receive treatment as usual (TAU). Efficacy improvement is greatest for patients on multiple medications (likely to be treatment-resistant), and those identified by the test to be taking problematic, red-binned drugs (data not shown). GeneSightRx® is a rapid and effective pharmacogenomic decision support tool, and can be used for cohort stratification prior to clinical trials.
  • 13. AssureRx Health, Inc. CONFIDENTIAL 13
  • 14. Demogenics of 17,131 human genome sequences AssureRx Health, Inc. CONFIDENTIAL 14
  • 15. How do we process all of these sequences? Data production Data storage, manipulation Data annotation, interpretation Report generation
  • 16. AssureRx Health, Inc. CONFIDENTIAL 16
  • 17. Lee Hood, IOM February 27, 2012
  • 18. Trends in NGS and Drug Development 1. Precompetitive data sharing using collaborative informatics: • tranSMART • TransCelerate BioPharma 2. Nanopore-based, single molecule sequencing. 1. Improved understanding of human variation of all types– “it isn't just the SNPs anymore.” AssureRx Health, Inc. CONFIDENTIAL 18
  • 19. Applications in Drug Discovery “The ideal nucleic acid sequencing technology for drug discovery and development should: • Sequence natural DNA/RNA fragments of various sizes fully with minimal (or no) errors • Haplotype phasing on a chromosome scale; • Generate no sequence-dependent or other biases; • Require minimum quantities of input material, ideally single cells; • Have high/complete efficiency in all of the sequencing steps; • Detect modified nucleotides (such as methylated cytosines) directly; • Operate in laboratories and low-resource settings without special external environment requirements such as temperature and humidity control.” – Mike Braxenthaler, Roche and Pistoia Alliance AssureRx Health, Inc. CONFIDENTIAL 19
  • 20. The Biggest Problem we can’t solve Potential for Drug-Drug Interactions! Number of Patients Aged 18-24 / VA Med. Ctr. Average number of prescription drugs per day 3,125 5,860 6,001 12, 392 average average average average number of number of number of number of drugs each drugs each drugs each drugs each day =19 day = 15 day = 12 day = 7 AssureRx Health, Inc. CONFIDENTIAL 20

Notes de l'éditeur

  1. Prevalence of mental illness (NIMH 2009):Eating disorders 1-3% of population (includes three basic types: anorexia nervosa, bulimia nervosa and binge-eating disorder). 90% female. While it’s not a highly prevalent disorder, it is deadly. Over a decade, the mortality rate for people with anorexia is 5.6% which is about 12 times higher than the annual death rate due to all causes of death among females age 15-24. PTSD: 3.5% or 7.7 M AmericansADHD: one of most common disorders in children and adolescents also affect 4.1% adults in a given yearMood Disorders include all forms of depression and bipolar disorder 9.5% or 20.9 million adults in a given year have a mood disorderAnxiety Disorders: include panic disorder, general anxiety disorder, OCD,phobias 33 million peopleFor comparisonAll forms of Cancer 3.7% or 11 millionDiabetes 8% or 23.5 million Statistics from the American Heart Association Estimates for the year 2006 gave the breakdown for that year as follows - In 2006, among those who had heart disease, approximately 73.6 million suffered from high blood pressure, 16.8 million had coronary artery disease (i.e. had experienced an acute heart attack or had active angina or chest pain), 6.5 million had dealt with a stroke, and 5.7 million had experienced heart failure.  American Cancer FoundationAmerican Diabetes AssociationAmerican Heart Association
  2. Prevalence of mental illness (NIMH 2009):Eating disorders 1-3% of population (includes three basic types: anorexia nervosa, bulimia nervosa and binge-eating disorder). 90% female. While it’s not a highly prevalent disorder, it is deadly. Over a decade, the mortality rate for people with anorexia is 5.6% which is about 12 times higher than the annual death rate due to all causes of death among females age 15-24. PTSD: 3.5% or 7.7 M AmericansADHD: one of most common disorders in children and adolescents also affect 4.1% adults in a given yearMood Disorders include all forms of depression and bipolar disorder 9.5% or 20.9 million adults in a given year have a mood disorderAnxiety Disorders: include panic disorder, general anxiety disorder, OCD,phobias 33 million peopleFor comparisonAll forms of Cancer 3.7% or 11 millionDiabetes 8% or 23.5 million Statistics from the American Heart Association Estimates for the year 2006 gave the breakdown for that year as follows - In 2006, among those who had heart disease, approximately 73.6 million suffered from high blood pressure, 16.8 million had coronary artery disease (i.e. had experienced an acute heart attack or had active angina or chest pain), 6.5 million had dealt with a stroke, and 5.7 million had experienced heart failure.  American Cancer FoundationAmerican Diabetes AssociationAmerican Heart Association