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.
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.
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
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
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